Expression of Inducible Nitric Oxide Synthase Is Increased in Rat Barrett's Esophagus Induced by Duodenal Contents Reflux

Abstract

Barrett's esophagus is a premalignant condition of esophageal adenocarcinoma. Inducible nitric oxide synthase (iNOS) is induced by cytokines and can generate locally high concentrations of nitric oxide (NO), whose metabolites can mediate genotoxicity and influence multistage carcinogenesis by causing DNA damage. Therefore, we evaluated the immunolocalization and expression of iNOS in surgically induced rat Barrett's esophagus. Esophagoduodenal anastomosis was performed in rats for inducing reflux of duodenal contents. Rats were killed at postoperative 10, 20, 30 and 40 weeks. We examined histologic changes and iNOS expression in esophagus by immunohistochemistry and reverse transcription-polymerase chain reaction. Eighty six percent of experimental rats showed Barrett's esophagus above esophagoduodenal junction. iNOS immunoreactivity was clearly observed in the epithelial cells of Barrett's esophagus, predominantly at the apical surface of epithelial cells. Cytoplasmic staining was also seen only in atypical Barrett's esophagus. iNOS mRNA was detected only in the lower esophagus of experimental group. In conclusion, this study suggests that iNOS has some roles on Barrett's esophagus formation.

Molecular mechanisms of acid exposure in Barrett’s esophagus

“…In fact, iNOS expression has been found in the specialized intestinal epithelial cells in a rat model of refl ux and Barrett's esophagus (Bae et al, 2005). Moreover, iNOS expression has been found in biopsies of non-dysplastic specialized intestinal metaplasia, Barrett's with dysplasia, and esophageal adenoncarcinoma (van der Woude et al, 2002;Wilson et al, 1998).…”

Natural development of Barrett’s oesophagus and adenocarcinoma in experimental models of gastroesophageal reflux disease

“…polega na wykonaniu całkowitej gastrektomii z zespoleniem końca przełyku z boczną ścianą jelita czczego w odległości 4 cm od więzadła Treitza [7]. Metodę polegającą na wykonaniu zespolenia końca przełyku z bokiem jelita czczego bez resekcji żołądka opracowali Lewrat i Clark [22][23][24]. Według Naito i wsp.…”

The role of nitric oxide in the induction of caudal-type homeobox 2 through epidermal growth factor receptor in the development of Barrett's esophagus

“…Nitric oxide is also known to play key roles as a mediator of ROS-induced signaling [14,20,21] through interaction with plasma membranous proteins and subsequent activation of intracellular signaling cascades. One of these plasma membranous receptors that can interact with NO is epithelial growth factor receptor (EGFR), a 170-kDa glycoprotein that is a member of the receptor tyrosine kinase superfamily [1,3,[34][35][36][37].…”

“…In view of the process of their generation, NO is classified into two groups, endogenous and exogenous [21]. In endogenous NO, constitutive nitric oxide synthase expressed constitutively is involved in the production of small amounts of NO, and inducible nitric oxide synthase (iNOS) derived from stimulation by inflammatory cytokines produces large amounts of NO [21,22]. Exogenous NO is generated by the acidification of nitrite within the lumen of the upper-gastrointestinal tract [23][24][25].…”

“…The large amount of NO can easily react with superoxide and contribute to the production of peroxynitrite. In view of the process of their generation, NO is classified into two groups, endogenous and exogenous [21]. In endogenous NO, constitutive nitric oxide synthase expressed constitutively is involved in the production of small amounts of NO, and inducible nitric oxide synthase (iNOS) derived from stimulation by inflammatory cytokines produces large amounts of NO [21,22].…”